Hypomyelination and congenital cataract is an inherited condition that affects the nervous system and the eyes. This disease is one of a group of genetic disorders called leukoencephalopathies. Leukoencephalopathies involve abnormalities of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. Hypomyelination and congenital cataract is caused by a reduced ability to form myelin (hypomyelination). Additionally, people with this disorder are typically born with a clouding of the lens (cataract) in both eyes.

People with this condition usually have normal development throughout the first year of life. Development slows around the age of 1. Most affected children learn to walk between the ages of 1 and 2, although they usually need some type of support. Over time they experience muscle weakness and wasting (atrophy) in their legs, and many affected people eventually require wheelchair assistance. Weakness in the muscles of the trunk and a progressive abnormal curvature of the spine (scoliosis) further impair walking in some individuals. Most people with hypomyelination and congenital cataract have reduced sensation in their arms and legs (peripheral neuropathy). In addition, affected individuals typically have speech difficulties (dysarthria) and mild to moderate intellectual disability.

Variants (also called mutations) in the HYCC1 gene cause hypomyelination and congenital cataract. The HYCC1 gene provides instructions for making a protein called hyccin, the function of which is not completely understood. Based on the features of hypomyelination and congenital cataract, researchers presume that hyccin is involved in the formation of myelin throughout the nervous system. Hyccin is also active in the lens of the eye, the heart, and the kidneys. It is unclear how variants in the HYCC1 gene cause cataracts.

Most HYCC1 gene variants that cause hypomyelination and congenital cataract prevent the production of hyccin. People who cannot produce any hyccin have problems forming myelin, leading to the signs and symptoms of this condition.

People who have variants that allow some protein production tend to have milder symptoms than those who produce no protein. These individuals typically retain the ability to walk longer, although they still need support, and they usually do not have peripheral neuropathy.

Normal Function

The HYCC1 gene provides instructions for making a protein called hyccin, which is active (expressed) throughout the nervous system. Researchers believe that hyccin is involved in the formation of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Hyccin is also active in the lens of the eye, the heart, and the kidneys; however, the protein's function in these tissues is unclear.

Health Conditions Related to Genetic Changes

Hypomyelination and congenital cataract

At least four variants (also called mutations) in the HYCC1 gene have been found to cause hypomyelination and congenital cataract. Most variants delete a large portion of the gene or create a premature stop signal in the instructions for making hyccin. These variants prevent the production of any functional protein. One HYCC1 gene variant allows some protein to be produced. This variant replaces the protein building block (amino acid) leucine with the amino acid proline at position 53 in the hyccin protein (written as Leu53Pro or L53P). People with the Leu53Pro variant tend to have milder symptoms than those with variants that prevent the production of any protein.

Any disruption in the production of hyccin impairs its role in the formation of myelin, leading to neurological problems such as intellectual disability and walking difficulties. It is unclear how a lack of hyccin causes a clouding of the lens (cataract) in both eyes that is typically present from birth in affected individuals. The neurological problems and cataracts are the characteristic features seen in people with hypomyelination and congenital cataract.

Other Names for This Gene

• DRCTNNB1A
• FAM126A
• HCC
• HLD5
• HYCC1
• HYCCI_HUMAN

Genomic Location

The HYCC1 gene is found on chromosome 7.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

The prevalence of hypomyelination and congenital cataract is unknown.